The aim of this pilot study is the induction of hyperkeratosis without atypia in the cheek pouch of hamsters by repeated painting of the pouch with turpentine in heavy mineral oil, using the method of Craig and Franklin (1,2). With the successful application of that method, we intend to initiate a long-term study of epithelial cell physiology (histochemistry, biochemistry and cell kinetics) in keratotic lesions of the oral cavity. Although keratoses are among the most common lesions of the oral mucosa, there are very few physiologic studies of such lesions. Keratoses, even with no atypia, are cause for concern because they indicate that the oral epithelium in the affected individual responds in an abnormal manner to a stimulus; for example, only a small proportion of individuals who smoke develop keratotic lesions. Treatment is indicated because this response may later develop into a more serious lesion, including carcinoma. Some of the keratoses respond to pharmaceutical treatment, but a large number resist any form of non-surgical intervention. An understanding of the physiologic processes involved may lead to more effective pharmaceutical treatment of the lesions. Four groups of experimental hamsters will be used. A 50 percent solution of turpentine in heavy mineral oil will be applied repeatedly to one pouch of each hamster. The other pouch will serve as one control and will be painted with mineral oil only. Experimental periods will be 6, 9, 12 or 15 weeks in order to determine when significant hyperkeratosis is achieved. A group of age-matched hamsters, receiving no experimental intervention, will serve as a second control. After the time required for significant hyperkeratosis to develop is determined, turpentine will be applied to the pouches of a separate group of hamsters for that time and then the application will cease. Pouches will be taken at two-day intervals for twelve days in order to determine for how long significant hyperkeratosis persists in the absence of turpentine painting. All tissues will be examined light-microscopically for thickness of the stratum corneum and the thickness of the nucleated part of the epithelium, for inflammation, and for signs of epithelial atypia.